Adherence to antiretroviral treatment (ART) is a key clinical challenge in the care of persons living with HIV (PLWH). Although much is known about the costs, consequences, and correlates of ART nonadherence, less is known about its causes or solutions. Furthermore, several reviews have concluded that interventions based on existing theories of adherence produce weak and inconsistent results. Most prior research has treated adherence as constant over time and has studied it in relationship to stable demographic variables or psychological traits, which are long-term and relatively stable patterns of interpreting and responding to events with possible genetic underpinnings. But because ART adherence varies within persons over time, it instead can be studied in relationship to momentary states, which are temporary psychological experiences that vary over the course of everyday life. In the current study, PLWH will complete daily electronic questionnaires about momentary state variables, using technology that is acceptable to PLWH and not burdensome based on our pilot research. Once each day at randomly cued times, PLWH will complete a brief psychological survey. They will also be asked to store their ART medication in a MEMS bottle, which will unobtrusively track their adherence during the same time period. MEMS data will be linked via date- and time-stamps to the daily survey data. Based on an integrative, multidisciplinary model of adherence developed from prior research, we hypothesize that five momentary state variables - control beliefs, mood, stress, coping, and social support - will predict adherence behavior. We will test whether each of these momentary state variables predicts adherence, and will compare effect sizes for these state variables to those of the best trait-level predictors identified in our team's meta-analysis of prior ART adherence research (Aim 1). The comparison of state and trait predictors' effects will be a unique contribution to the adherence literature. In addition, our study will test a predicted mediating effect of momentary motivation as a mechanism by which momentary states affect adherence behavior (Aim 2). Understanding the role of motivation will help to differentiate between intentional and unintentional nonadherence. Consistent with the goals of PA-10-069, this study offers the potential for major long-term impact through the unique and innovative application of existing research methods (daily electronic data collection and multilevel modeling analysis) to a new area of health behavior research (antiretroviral medication adherence). Ultimately, knowledge of the barriers and facilitators of adherence that PLWH experience in their everyday lives will inform the future development of tailored messaging interventions that target momentary states. Findings also can be used to educate HIV care providers about the everyday experiences that impact patients' ART adherence. Finally, findings about the effects of momentary states on ART adherence may have future applicability to studies of medication adherence in other chronic diseases and to other types of health behavior change. PUBLIC HEALTH RELEVANCE: This study's immediate impact will be to provide a new way for health care providers to understand patients' medication adherence based on their momentary states, which are temporary and changeable psychological experiences in the course of daily life. Findings about the role of momentary states in ART adherence can then be used to develop innovative in-the-moment interventions to improve ART adherence and health for the >1 million persons living with HIV (PLWH) in the United States, by delivering tailored messages that target the specific momentary states most strongly related to ART adherence. A model that predicts adherence from momentary states will also have the potential for major long-term impact by facilitating understanding and novel tailored-messaging adherence interventions for the estimated 50% of Americans who currently take medications for other chronic diseases.